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As I'm going to argue repeatedly
today, biology has become a science
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over the last 50 years. And,
as a consequence, we can talk
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about some basic principles.
We can talk about some laws and
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then begin to apply them to very
interesting biological problems.
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And so our general strategy this
semester, as it has been in the past,
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is to spend roughly the first half
of the semester talking about the
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basic laws and rules that govern
all forms of biological life
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on this planet. And you
can see some of the specific
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kinds of problems, including
the problem of cancer,
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how cancer cells begin to grow
abnormally, how viruses proliferate,
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how the immune system functions,
how the nervous system functions,
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stem cells and how they work and
their impact on modern biology,
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molecular medicine, and finally
perhaps the future of biology and
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even certain aspects of evolution.
The fact of the matter is that we
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now understand lots of these things
in ways that were inconceivable 50
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years ago. And now we could begin
to talk about things that 50 years
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ago people could not have dreamt of.
When I took this course, and I did
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take it in 1961, we didn't
know about 80% of what we
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now know. You cannot
say that about mechanics
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in physics, you cannot say that
about circuit theory in electronics,
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and you cannot say that,
obviously, about chemistry.
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And I'm mentioning that to you
simply because this field has
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changed enormously over the ensuing
four decades. I won't tell you what
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grade I got in 7. 1
because if I would,
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and you might pry it out
of me later in the semester,
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you probably would never
show up again in lecture.
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But in any case, please
know that this has been an
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area of enormous ferment. And
the reason it's been in such
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enormous ferment is of the discovery
in 1953 by Watson and Crick of the
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structure of the DNA double helix.
Last year I said that we were so
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close to this discovery that both
Watson and Crick are alive and with
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us and metabolically active,
and more than 50 years, well,
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exactly 50 years after the discovery.
Sadly, several months ago one of the
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two characters, Francis
Crick died well into his
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eighties, and so he is no longer
with us. But I want to impress on
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you the notion that 200 years from
now, we will talk about Watson and
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Crick the same way that people
talk about Isaac Newton in terms of
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physics. And that will be so
because we are only beginning to
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perceive the ramifications of
this enormous revolution that was
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triggered by their discovery.
That is the field of molecular
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biology and genetics and
biochemistry which has totally
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changed our perceptions of how
life on Earth is actually organized.
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Much of the biology to which you
may have been exposed until now has
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been a highly descriptive science.
That is you may have had courses in
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high school where you had to
memorize the names of different
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organisms, where you had to
understand how evolutionary
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phylogenies were organized, where
you had to learn the names of
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different organelles, and
that biology was, for you,
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a field of memorization.
And one point we would like,
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hopefully successfully, to drive
home this semester is the notion
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that biology has now achieved a
logical and rational coherence that
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allows us to articulate a whole set
of rules that explain how all life
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forms on this planet are organized.
It's no longer just a collection of
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jumbled facts. Indeed,
if one masters these
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molecular and genetic principles,
one can understand in principle a
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large number of processes that exist
in the biosphere and begin to apply
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one's molecular biology to
solving new problems in this arena.
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One of the important ideas that
we'll refer to repeatedly this
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semester is the fact that many of
the biological attributes that we
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posses now were already developed
a very long time ago early in the
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inception of life on this planet.
So if we look at the history of
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Earth, here the history of Earth
is given as 5 billion years,
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this is in thousands obviously.
The Earth is probably not that old.
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It's probably 4.5 or 4 or
3 billion years but, anyhow,
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that's when the planet first
aggregated, as far as we know.
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One believes that no life existed
for perhaps the first half billion
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years, but after half a billion
years, which is a lot of time to be
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sure, there already begins to be
traces of life forms on the surface
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of this planet.
And that, itself,
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is an extraordinary testimonial,
a testimonial to how evolutionary
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processes occur. We don't
know how many planets
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there are in the universe
where similar things happened.
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And we don't know whether the
solution that were arrived at by
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other life systems in other
places in the universe,
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which we may or may not ever
discover, were the similar solutions
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to the ones that have
been arrived at here.
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It's clear, for example, that
to the extent that Darwinian
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Evolution governs the development
of life forms on this planet that is
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not an artifact of the Earth.
Darwinian Evolution is a logic
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which is applicable to all life
forms and all biosystems that may
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exist in the universe, even
the ones we have not discovered.
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However, there are specific
solutions that were arrived at
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during the development of life on
Earth which may be peculiar to Earth.
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The structure of
the DNA double helix.
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The use of ribose in deoxyribose.
The choice of amino acids to make
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proteins. And those specific
solutions may not be universal.
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Whether they're universal in the
sense of existing in all life forms
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across the planet, the
fact is that many of the
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biochemical and molecular solutions
that are represented in our own
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cells today, these solutions,
these problems were solved already 2
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and 3 billion years ago. And
once they were solved they were
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kept and conserved almost unchanged
for the intervening 2 or 3 billion
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years. And that strong degree of
conservation means that we can begin
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to figure out what these principles
were early on in evolution of life
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on this planet and begin to apply
them to all modern life forms.
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From the point of view of evolution,
almost all animals are identical in
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terms of their biochemistry and
in terms of their physiology.
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The molecular biology
of all eukaryotic cells,
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that is all cells that have
nuclei in them, is almost the same.
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And, therefore, we're not going
to focus much in this course this
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semester on specific species but
rather focus on general principles
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that would allow us to understand
the cells and the tissues and the
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physiological processes that are
applicable to all species on the
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surface of the planet. Let's
just look here and get us
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some perspective on this because,
the fact of the matter is, is that
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multicellular life forms, like
ourselves, we have, the average
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human being has roughly three
or four or five times ten to the
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thirteenth cells in the body.
That's an interesting figure.
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The average human being goes
through roughly ten to the sixteenth
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cell divisions in a lifetime,
i.e. ten to the sixteenth times in
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your body there will be cells
that divide, grow and divide.
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Every day in your body there are
roughly ten to the eleventh cells
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that grow and divide. Think
of that, ten to the eleventh.
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And you can divide that by the
number of minutes in a day and come
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up with an astounding degree of
cellular replication going on.
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All of these processes can be
traceable back to solutions that
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were arrived at very early in the
evolution of life on this planet,
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perhaps 550, 600 million years ago
when the first multicellular life
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forms began to evolve. Before
that time, that is to say
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before 500 to 600 million years ago,
there were single-cell organisms.
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For example, many of them survive
to this day. There were yeast-like
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organisms. And there were bacteria.
And we make one large and major
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distinction between the two major
life forms on the planet in terms of
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cells. One are the prokaryotic
cells. And these are the cells of
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bacteria, I'll show you an image
of them shortly, which lack nuclei.
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And the eukaryotic cells which
poses nuclei and indeed have a highly
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complex cytoplasm and
overall cellular architecture.
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We think that the prokaryotic life
forms on this planet evolved first
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probably on the order of 3
billion years ago, maybe 3.
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billion years ago, and that about
1. billion years ago cells evolved
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that contained nuclei.
Again, I'll show them to you
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shortly. And these
nucleated cells,
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the eukaryotes then existed in
single-cell form for perhaps the
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next 700 or 800 million years
until multi-cellular aggregates of
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eukaryotic cells first assembled
to become the ancestors of the
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multi-cellular plants and the
multi-cellular animals that exist on
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the surface of the Earth today.
To put that in perspective, our
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species has only been on
the planet for about 150,
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00 years. So we've all been
here for that period of time.
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And a 150,000 sounds like
a long time, in one sense,
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but it's just “a blink in the eye
of the Lord” as one says in terms of
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the history of life on this planet,
and obviously the history of the
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universe which is somewhere
between 13 and 15 billion years old.
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You can begin to see that the
appearance of humans represents a
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very small segment of the entire
history of life on this planet.
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And here you can roughly see the way
that life has developed during this
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period of time from the fossil
record. You see that many plants
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actually go back a reasonable length
of time, but not more than maybe 300
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or 400 million years.
Here are the Metazoa.
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And this
represents --
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Well, can you hear me?
Wow, 614 came in handy.
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OK. So if we talk about
another major division,
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we talk about protozoa and metazoa.
The suffix zoa refers to animals,
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as in a zoo. And the protozoa
represents single-cell organisms.
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The metazoa represent multi-cellular
organisms. And we're going to be
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focusing largely on the biology
of metazoan cells this semester,
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and we're going to be spending
almost no time on plants.
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It's not that plants aren't
important. It's just that we don't
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have time to cover everything.
And, indeed, the molecular biology
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that you learn this semester will
ultimately enable you to understand
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much about the physiology of
multi-cellular plants which happen
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to be called metaphyta, a term
you may never hear again in
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your entire life after
today. That reminds me,
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by the way, that both Dr. Lander
and I sometimes use big words.
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And people come up to me afterwards
each semester each year and say
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Professor Weinberg, why
don't you talk simple,
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why don't you talk the way we
heard things in high school?
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And please understand that if I use
big words sometimes it's to broaden
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your vocabulary so you
can learn big words.
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One of the things you should be able,
one of the big take-home lessons of
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this course should be that
your vocabulary is expanded.
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Not just your scientific vocabulary
but your general working English
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vocabulary. Perhaps the
biggest goal of this course,
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by the way, is not that you learn
the names of all the organelles and
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cells but that you learn how to
think in a scientific and rational
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way. Not just because of this
course but that this course
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helps you to do so. And as
such, we don't place that
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much emphasis on memorization but
to be able to think logically about
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scientific problems. Here
we can begin to see the
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different kinds of metazoa, the
animals. Here are the metaphyta
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and here are the protozoa,
different words for all of these.
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And here we see our own
phylum, the chordates. And,
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again, keep in mind that this line
right down here is about 550 to 600
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million years ago, just to
give you a time scale for
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what's been going
on, on this planet.
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One point we'll return to repeatedly
throughout the semester is that all
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life forms on this planet
are related to one another.
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It's not as if life was invented
multiple times on this planet and
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that there are multiple independent
inventions to the extent that life
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arose more than once on this
planet, and it may have. The other
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alternative or competing life forms
were soon wiped out by our ancestors,
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our single-cellular
ancestors 3 billion years ago.
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And, therefore, everything
that exists today on this
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planet represents the descendents of
that successful group of cells that
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existed a very long time ago.
Here we have all this family tree
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of the different metazoan forms that
have been created by the florid hand
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of evolution. And we're not going
to study those phylogenies simply
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because we want to understand
principles that explain all of them.
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Not just how this or that particular
organism is able to digest its food
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or is able to reproduce.
Here's another thing we're not
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going to talk about. We're
not going to talk about
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complicated life forms. We're
not going to talk very much,
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in fact hardly at all, about
ecology. This is just one such thing,
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the way that a parasite is able to,
a tapeworm is able to infect people.
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This is, again, I'm showing you
this not to say this is what we're
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going to talk about, we're
not going to talk about that.
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We're not going to talk about that.
There's a wealth of detail that's
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known about the way life exists
in the biosphere that we're simply
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going to turn our backs on by
focusing on some basic principles.
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We're also not going to talk about
anatomy. Here in quick order are
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some of the anatomies you may
have learned about in high school,
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and I'm giving them to you
each with a three-second minute,
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a three-second showing to say
we're not going to do all this.
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And rather just to reinforce
our focus, we're going to limit
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ourselves to a very finite
part of the biosphere.
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And here is one way of depicting
the biosphere. It's obviously an
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arbitrary way of doing so
but it's quite illustrative.
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Here we start from molecules.
And, in fact, we will occasionally
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go down to submolecular atoms.
And here's the next dimension of
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complexity, organelles. That
is these specialized little
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organs within cells. We're
going to focus on them as
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well. We're going to focus on
cells. And when we start getting to
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tissues, we're going to start
not talking so much about them.
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And we're not going to talk about
organisms and organs or entire
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organisms or higher complex
ecological communities.
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And the reason we're doing that is
that for 40 years in this department,
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and increasingly in the rest of the
world there is the acceptance of the
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notion that if we understand what
goes on down here in these first
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three steps, we can understand
almost everything else in principle.
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Of course, in practice we may not
be able to apply those principles to
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how an organism works or to
how the human brain works yet.
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Maybe we never will. But,
in general, if one begins to
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understand these principles down
here, one can understand much about
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how organismic embryologic develop
occurs, one can understand a lot
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about a whole variety of disease
processes, one can understand how
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one inherits disease susceptibilities,
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and one can understand why many
organisms look the way they do,
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i.e. the process of
developmental biology.
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And so, keep in mind that if you
came to hear about all of these
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things, we're going to let you down.
That's not what this is going to be
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about. This also dictates the
dimensions of the universe that
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we're going to talk about because
we're going to limit ourselves to
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the very, very small and not to
the microscopic. On some occasions
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we'll limit ourselves to items that
are so small you cannot see them in
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the light microscope. On other
occasions we may widen our
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00:17:36 --> 00:17:40
gaze to look at things that
are as large as a millimeter,
247
00:17:40 --> 00:17:45
but basically we're staying very,
very small. Again, because we view,
248
00:17:45 --> 00:17:50
correctly or not, the fact that the
big processes can be understood by
249
00:17:50 --> 00:17:54
delving into the molecular details
of what happens invisibly and cannot
250
00:17:54 --> 00:17:59
be seen by most ways of visualizing
things, including the light and
251
00:17:59 --> 00:18:04
often even the electron microscope.
Keep in mind that 50 years ago we
252
00:18:04 --> 00:18:08
didn't know any of this,
for all practical purposes,
253
00:18:08 --> 00:18:12
or very little of this. And keep
in mind that we're so close to this
254
00:18:12 --> 00:18:16
revolution that we don't really
understand its ramifications.
255
00:18:16 --> 00:18:21
I imagine it will be another 50
years before we really begin to
256
00:18:21 --> 00:18:25
appreciate the fallout, the
long-term consequences of this
257
00:18:25 --> 00:18:29
revolution in biology which began
51 years ago. And so you're part of
258
00:18:29 --> 00:18:34
that and you're going to experience
it much more than my generation did.
259
00:18:34 --> 00:18:38
And indeed one of the reasons why
MIT decided about 10 or 12 years ago
260
00:18:38 --> 00:18:42
that every MIT undergraduate needed
to have at least one semester of
261
00:18:42 --> 00:18:47
biology is that biology, in
the same way as physics and
262
00:18:47 --> 00:18:51
chemistry and math, has become
an integral part of every
263
00:18:51 --> 00:18:55
educated person's knowledge-base in
terms of their ability to deal with
264
00:18:55 --> 00:18:59
the world in a rational way.
In terms of public policy,
265
00:18:59 --> 00:19:03
in terms of all kinds of ethical
issues, they need to understand
266
00:19:03 --> 00:19:06
what's really going on. Many
of the issues that one talks
267
00:19:06 --> 00:19:09
about today about bioethics are
articulated by people who haven't
268
00:19:09 --> 00:19:13
the vaguest idea about what
we're talking about this semester.
269
00:19:13 --> 00:19:16
You will know much more than they
will, and hopefully some time down
270
00:19:16 --> 00:19:20
the road, when you become more and
more influential voices in society,
271
00:19:20 --> 00:19:23
you'll be able to contribute
what you understood here,
272
00:19:23 --> 00:19:27
what you learned here
to that discussion.
273
00:19:27 --> 00:19:31
Right now much of bioethical
discussion is fueled by people who
274
00:19:31 --> 00:19:35
haven't the vaguest idea what a
ribosome or mitochondrion or even a
275
00:19:35 --> 00:19:39
gene is, and therefore is often
a discussion of mutually shared
276
00:19:39 --> 00:19:43
ignorance which you can
diffuse by learning some basics,
277
00:19:43 --> 00:19:47
by learning some of the essentials.
Here is the complexity of the cell
278
00:19:47 --> 00:19:51
we're going to focus on largely
this semester, which is to say the
279
00:19:51 --> 00:19:55
eukaryotic rather than
the prokaryotic cell.
280
00:19:55 --> 00:19:59
And this is just to give you a
feeling for the overall dimensions
281
00:19:59 --> 00:20:03
of the cell and refer to many of
the landmarks that will repeatedly be
282
00:20:03 --> 00:20:08
brought up during the
course of this semester.
283
00:20:08 --> 00:20:11
Here is the nucleus. The
term karion comes from the
284
00:20:11 --> 00:20:15
Greek meaning a seed or a kernel.
And the nucleus is what gives the
285
00:20:15 --> 00:20:19
eukaryotic cell its name.
Within the nucleus, although not
286
00:20:19 --> 00:20:22
shown here, are the
chromosomes which carry DNA.
287
00:20:22 --> 00:20:26
You may have learned that a long
time ago. Outside of the nucleus is
288
00:20:26 --> 00:20:30
this entire vast array of organelles
that goes from the nuclear membrane,
289
00:20:30 --> 00:20:34
and I'm point to it right here,
all the way out to the outside
290
00:20:34 --> 00:20:37
of the cell. The outside
limiting membrane,
291
00:20:37 --> 00:20:41
the outer membrane of the cell
is called the plasma membrane.
292
00:20:41 --> 00:20:44
And between the nucleus and the
plasma membrane there is an enormous
293
00:20:44 --> 00:20:48
amount of biological and
biochemical activity taking place.
294
00:20:48 --> 00:20:52
Here are, for example,
the mitochondria. And the
295
00:20:52 --> 00:20:55
mitochondria, as one has learned,
are the sources of energy production
296
00:20:55 --> 00:20:59
in the cell. And, therefore,
we'll touch on them very
297
00:20:59 --> 00:21:03
briefly. This is an
artist's conception of
298
00:21:03 --> 00:21:07
what a mitochondrion looks like.
Almost always artists' conceptions
299
00:21:07 --> 00:21:12
of these things have only vague
resemblance to the reality.
300
00:21:12 --> 00:21:16
But, in any case, you can begin to
get a feeling for what one thinks
301
00:21:16 --> 00:21:21
about their appearance. Here
are mitochondria sliced open
302
00:21:21 --> 00:21:25
by the hand of the artist.
And, interestingly, mitochondria
303
00:21:25 --> 00:21:30
have their own DNA in them.
One now accepts the fact that
304
00:21:30 --> 00:21:34
mitochondria are the descendents of
bacteria which insinuated themselves
305
00:21:34 --> 00:21:39
into the cytoplasms of larger cells,
roughly 1.5 billion years ago, and
306
00:21:39 --> 00:21:43
began to do a specialized job
which increasingly became the job of
307
00:21:43 --> 00:21:47
energy production within cells.
To this day, mitochondria retain
308
00:21:47 --> 00:21:51
some vestigial attributes of the
bacterial ancestors which initially
309
00:21:51 --> 00:21:54
colonized or parasitized
the cytoplasm of the cell.
310
00:21:54 --> 00:21:58
When I say parasitized,
you might imagine that the
311
00:21:58 --> 00:22:02
mitochondria are taking
advantage of the cell.
312
00:22:02 --> 00:22:06
But, in fact, the mitochondria
represent the essential sources of
313
00:22:06 --> 00:22:11
energy production in the cell.
Without our mitochondria, as you
314
00:22:11 --> 00:22:16
might learn by taking cyanide, for
example, you don't live for very
315
00:22:16 --> 00:22:20
many minutes. And the vestiges of
bacterial origins of mitochondria
316
00:22:20 --> 00:22:25
are still apparent in the fact that
mitochondria still have their own
317
00:22:25 --> 00:22:30
DNA molecule, their own chromosome.
They still have their own ribosomes
318
00:22:30 --> 00:22:34
and protein synthetic apparatus,
even though the vast majority of the
319
00:22:34 --> 00:22:39
proteins inside mitochondria
are imported from the cytoplasm,
320
00:22:39 --> 00:22:43
i.e., these vestigial bacteria now
rely on proteins made by the cell at
321
00:22:43 --> 00:22:48
large that are imported into the
mitochondrion to supplement the
322
00:22:48 --> 00:22:53
small number of vestigial bacterial
proteins which are still made here
323
00:22:53 --> 00:22:57
inside the mitochondrion and
used for essential function
324
00:22:57 --> 00:23:01
in energy production. Here
is the Golgi apparatus.
325
00:23:01 --> 00:23:05
And the Golgi apparatus up here is
used for the production of membranes.
326
00:23:05 --> 00:23:08
As one will learn throughout the
semester, the membranes of a cell
327
00:23:08 --> 00:23:12
are in constant flux and are
being pulled in and remodeled and
328
00:23:12 --> 00:23:15
regenerated. The Golgi apparatus
is very important for that.
329
00:23:15 --> 00:23:19
Here's the rough endoplasmic
reticulum. That's important for the
330
00:23:19 --> 00:23:22
synthesis of proteins which are
going to be displayed on the surface
331
00:23:22 --> 00:23:26
of cells, you don't
see them depicted here,
332
00:23:26 --> 00:23:30
or are going to be secreted
into the extracellular space.
333
00:23:30 --> 00:23:33
Here are the ribosomes, which
I might have mentioned briefly
334
00:23:33 --> 00:23:37
before. And these ribosomes are the
factories where proteins are made.
335
00:23:37 --> 00:23:41
Again, we're going to
talk a lot about them. And,
336
00:23:41 --> 00:23:45
finally, several other aspects,
the cytoskeleton. The physical
337
00:23:45 --> 00:23:49
integrity, the architecture of
the cell is maintained by a complex
338
00:23:49 --> 00:23:53
network of proteins which
together are considered to be the
339
00:23:53 --> 00:23:57
cytoskeleton. And they enable
the cell to have some rigidity,
340
00:23:57 --> 00:24:01
to resist tensile forces,
and actually to move.
341
00:24:01 --> 00:24:04
Cells can actually move
from one place to the other.
342
00:24:04 --> 00:24:07
They have motile properties.
They're able to move from one
343
00:24:07 --> 00:24:11
location to another. The
process of cell motility,
344
00:24:11 --> 00:24:21
if that's a word
you'd like to learn.
345
00:24:21 --> 00:24:23
Here is what a prokaryotic
cell looks like by contrast.
346
00:24:23 --> 00:24:26
And I just want to give
you a feeling. First of all,
347
00:24:26 --> 00:24:28
it looks roughly like
a mitochondrion that I
348
00:24:28 --> 00:24:32
discussed before. But
you see that there is the
349
00:24:32 --> 00:24:36
absence of a nuclear membrane.
There's the absence of the highly
350
00:24:36 --> 00:24:41
complex cytoarchitecture.
Cyto always refers to cells.
351
00:24:41 --> 00:24:45
There's the absence of the complex
cytoarchitecture that one associates
352
00:24:45 --> 00:24:50
with eukaryotic cells. In
fact, all that a bacterium has
353
00:24:50 --> 00:24:54
is this area in the middle.
It's called the nucleoid, a term
354
00:24:54 --> 00:24:59
which you also will probably
never hear in your lifetime.
355
00:24:59 --> 00:25:02
And it represents simply an
aggregate of the DNA of the
356
00:25:02 --> 00:25:06
chromosomes of the bacterium.
And, in most bacteria, the DNA
357
00:25:06 --> 00:25:10
consists of only a single molecule
of DNA which is responsible for
358
00:25:10 --> 00:25:14
carrying the genetic information
of the bacteria. There's no membrane
359
00:25:14 --> 00:25:18
around this nucleoid. And
outside of this area where the
360
00:25:18 --> 00:25:22
DNA is kept are largely ribosomes
which are important for protein
361
00:25:22 --> 00:25:26
synthesis. There's a membrane
on the outside of this called the
362
00:25:26 --> 00:25:30
plasma membrane, very
similar to the plasma membrane
363
00:25:30 --> 00:25:34
of eukaryotic cells. And
outside of that is a meshwork
364
00:25:34 --> 00:25:38
that's called the outer membrane,
it's sometimes called the cell wall
365
00:25:38 --> 00:25:42
of the bacterium, which
is simply there to impart
366
00:25:42 --> 00:25:46
structural rigidity to the bacterium
making sure that it doesn't explode
367
00:25:46 --> 00:25:50
and holding it together. And
then there are other versions
368
00:25:50 --> 00:25:54
of eukaryotic cells. Here's
what a plant cell looks like.
369
00:25:54 --> 00:25:58
And it's almost identical to
the cells in our body, except
370
00:25:58 --> 00:26:02
for two major
features. For one thing,
371
00:26:02 --> 00:26:06
it has chloroplasts in it which
are also, one believes now,
372
00:26:06 --> 00:26:10
the vestiges of parasitic bacteria
that invade into the cytoplasm of
373
00:26:10 --> 00:26:14
eukaryotic cells. So, in
addition to mitochondria
374
00:26:14 --> 00:26:18
which are responsible for energy
production in all eukaryotic cells,
375
00:26:18 --> 00:26:22
we have here the chloroplasts which
are responsible for harvesting light
376
00:26:22 --> 00:26:26
and converting it into energy
in plant cells. The rest of the
377
00:26:26 --> 00:26:30
cytoplasm of a plant cell
looks pretty much the same.
378
00:26:30 --> 00:26:34
One feature that I didn't really
mention when I talked about an
379
00:26:34 --> 00:26:38
animal cell is in the middle of
the nucleus, here you can see,
380
00:26:38 --> 00:26:42
is a structure called a nucleolus.
And a nucleolus, or the nucleolus
381
00:26:42 --> 00:26:46
in the eukaryotic cell is
responsible for making the large
382
00:26:46 --> 00:26:50
number of ribosomes which are
exported from the nucleus into the
383
00:26:50 --> 00:26:54
cytoplasm. And, as I
mentioned just before,
384
00:26:54 --> 00:26:59
the ribosomes are responsible
for protein synthesis.
385
00:26:59 --> 00:27:03
It turns out this is a major
synthetic effort on the part of most
386
00:27:03 --> 00:27:07
cells. Cells, like our
own, have between 5 and 10
387
00:27:07 --> 00:27:11
million ribosomes in the cytoplasm.
So it's an enormous amount of
388
00:27:11 --> 00:27:15
biomass in the cytoplasm whose sole
function is to synthesize proteins.
389
00:27:15 --> 00:27:19
As we will learn also, proteins
that are synthesized by the
390
00:27:19 --> 00:27:23
ribosomes don't sit around forever.
Some proteins have long lives.
391
00:27:23 --> 00:27:27
Some proteins have lifetimes of
15 minutes before they're degraded,
392
00:27:27 --> 00:27:32
before they're turned over. One
other distinction between our
393
00:27:32 --> 00:27:36
cells, that is the cells
of metazoa and metaphyta,
394
00:27:36 --> 00:27:40
are the cell walls,
analogous to the cell walls of
395
00:27:40 --> 00:27:44
bacteria, this green thing on
the outside. As I said before,
396
00:27:44 --> 00:27:48
we do not have cell walls
around our cells. And we will,
397
00:27:48 --> 00:27:52
as the semester goes on, go
into more and more details about
398
00:27:52 --> 00:27:56
different aspects of this
cytoarchitecture during the first
399
00:27:56 --> 00:27:59
half of the semester.
Here, for example,
400
00:27:59 --> 00:28:03
is an artist's depiction of
the endoplasmic reticulum.
401
00:28:03 --> 00:28:07
Why it has such a complex name,
I cannot tell you, but it does.
402
00:28:07 --> 00:28:11
It's called the ER in the
patois of the street. The ER.
403
00:28:11 --> 00:28:14
And the endoplasmic reticulum
is a series of membranes.
404
00:28:14 --> 00:28:18
Keep in mind, not the only membrane
in the cell is the plasma membrane.
405
00:28:18 --> 00:28:22
Within the cytoplasm there are
literally hundreds of membranes
406
00:28:22 --> 00:28:26
which are folded up
in different ways.
407
00:28:26 --> 00:28:30
Here you see them depicted.
And one set of these membranes,
408
00:28:30 --> 00:28:34
often they're organized much like
tubes, represents the membranes of
409
00:28:34 --> 00:28:38
the endoplasmic reticulum which
either lacks ribosomes attached to
410
00:28:38 --> 00:28:43
it or has these ribosomes attached
to it which cause this to be called
411
00:28:43 --> 00:28:47
the rough endoplasmic reticulum to
refer to its rough structure which
412
00:28:47 --> 00:28:52
is created by the studding
of ribosomes on the surface.
413
00:28:52 --> 00:28:55
As we will learn, just
trying to give you a feeling
414
00:28:55 --> 00:28:59
for the geography of what we're
going to talk about this semester,
415
00:28:59 --> 00:29:03
these ribosomes on the surface
of the endoplasmic reticulum are
416
00:29:03 --> 00:29:07
dedicated to the task of making
highly specialized proteins which
417
00:29:07 --> 00:29:11
are either going to be dispatched
to the surface of the cell where they
418
00:29:11 --> 00:29:15
will be displayed on the cell's
surface or actually secreted into
419
00:29:15 --> 00:29:19
the extracellular space.
Many of the proteins that are
420
00:29:19 --> 00:29:23
destined for our body are not kept
within cells but are released into
421
00:29:23 --> 00:29:27
the extracellular space where
they serve important functions,
422
00:29:27 --> 00:29:31
and so we're going to
focus very much on them.
423
00:29:31 --> 00:29:35
Here's actually what some of these
things look like in the electron
424
00:29:35 --> 00:29:39
microscope to see whether we can
either believe or fully discredit
425
00:29:39 --> 00:29:43
the imaginations of the artists.
Here's the rough endoplasmic
426
00:29:43 --> 00:29:48
reticulum I showed you in schematic
form before. And you can see why
427
00:29:48 --> 00:29:52
it's called rough. All these
black dots are ribosomes
428
00:29:52 --> 00:29:56
attached on the outside.
Here's the Golgi apparatus.
429
00:29:56 --> 00:30:00
You see these vesicles
indicated here. And a vesicle,
430
00:30:00 --> 00:30:05
just to use a new word,
is simply a membranous bag.
431
00:30:05 --> 00:30:08
And keep in mind, by the
way, that we're not going to
432
00:30:08 --> 00:30:12
spend the semester with these
highly descriptive discussions.
433
00:30:12 --> 00:30:16
Our intent today is to get a lot of
these descriptive discussions out of
434
00:30:16 --> 00:30:19
the way so that we can begin to talk
in a common parlance about many of
435
00:30:19 --> 00:30:23
the parts, the molecular
parts of cells and organisms.
436
00:30:23 --> 00:30:27
Here is the mitochondrion
which we saw depicted before.
437
00:30:27 --> 00:30:31
It looks similar to, but
not identical to the artist's
438
00:30:31 --> 00:30:34
description of that.
And keep in mind that the
439
00:30:34 --> 00:30:38
mitochondrion in our cells,
as I said before, are the
440
00:30:38 --> 00:30:42
descendents of parasitic bacteria.
Here's the endoplasmic reticulum,
441
00:30:42 --> 00:30:46
and the way it would look, as
it does in certain parts of the
442
00:30:46 --> 00:30:49
cell when it doesn't have all
of these ribosomes studded on the
443
00:30:49 --> 00:30:53
surface. The endoplasmic reticulum
here is involved in making membranes.
444
00:30:53 --> 00:30:57
The endoplasmic reticulum here is
involved in the synthesis and export
445
00:30:57 --> 00:31:01
of proteins to the cell's
surface and for secretion, as
446
00:31:01 --> 00:31:05
I mentioned before. Much
of what we're going to talk
447
00:31:05 --> 00:31:09
about over the next days is going
to be focused on the nucleus of the
448
00:31:09 --> 00:31:14
cell, that is on the chromosomes on
the cell and on the material which
449
00:31:14 --> 00:31:19
is called chromatin which
carries the genetic material.
450
00:31:19 --> 00:31:23
So the term chromatin is used
in biology to refer simply to the
451
00:31:23 --> 00:31:28
mixture of DNA and proteins,
which together constitutes the
452
00:31:28 --> 00:31:33
chromosomes. So chromatin
has within it DNA,
453
00:31:33 --> 00:31:37
it has protein, and it has
a little bit of RNA in it.
454
00:31:37 --> 00:31:42
And we're going to focus mostly
on the DNA in the chromatin,
455
00:31:42 --> 00:31:46
because if we can begin to
understand the way the DNA works and
456
00:31:46 --> 00:31:51
functions many other
aspects will flow from that.
457
00:31:51 --> 00:31:55
I mentioned the cell's surface,
and I just want to impress on you
458
00:31:55 --> 00:32:00
the fact that the plasma membrane of
a cell is much more complicated than
459
00:32:00 --> 00:32:05
was depicted in these drawings
that I showed you just before.
460
00:32:05 --> 00:32:08
If we had a way of visualizing
the plasma membrane of a cell,
461
00:32:08 --> 00:32:12
we would discover that it's formed
from lipids. We see such lipids
462
00:32:12 --> 00:32:16
there, phospholipids, many
of them. We'll talk about them
463
00:32:16 --> 00:32:20
shortly. That the outside of the
cell, there are many proteins,
464
00:32:20 --> 00:32:24
you see them here, which thread
their way through the plasma
465
00:32:24 --> 00:32:28
membrane, have an extracellular
and intracellular part.
466
00:32:28 --> 00:32:32
And these transmembrane proteins,
which reach from outside to inside,
467
00:32:32 --> 00:32:36
represent a very important
way by which the cell senses
468
00:32:36 --> 00:32:39
its environment.
This plasma membrane,
469
00:32:39 --> 00:32:43
as we'll return to, represents a
very effective barrier to segregate
470
00:32:43 --> 00:32:47
what's inside the cell from what's
outside of the cell to increase
471
00:32:47 --> 00:32:51
concentrations of certain
biochemical entities.
472
00:32:51 --> 00:32:54
But at the same time it creates
a barrier to communication.
473
00:32:54 --> 00:32:58
And one of the things that cells
have had to solve over the last 700
474
00:32:58 --> 00:33:02
to 800 million years is ways by
which the exterior of the cell is
475
00:33:02 --> 00:33:06
able to send certain signals and
transmit that information to the
476
00:33:06 --> 00:33:09
interior of the cell.
At the same time,
477
00:33:09 --> 00:33:12
cells have had to use a number
of different, invent a number of
478
00:33:12 --> 00:33:16
different proteins, some
of them indicated here,
479
00:33:16 --> 00:33:19
which are able to transport
materials from the outside of the
480
00:33:19 --> 00:33:22
cell into the cell, or visa
versa. So the existence of
481
00:33:22 --> 00:33:25
the plasma membrane represents a
boon to the cell in the sense that
482
00:33:25 --> 00:33:29
it's able to segregate what's on the
inside from what's on the outside.
483
00:33:29 --> 00:33:33
But it represents an impediment to
communication which had to be solved,
484
00:33:33 --> 00:33:37
as well as an impediment to
transport. And many of these
485
00:33:37 --> 00:33:42
transmembrane proteins are dedicated
to solving those particular problems.
486
00:33:42 --> 00:33:46
Here you see, once again
an artist's depiction
487
00:33:46 --> 00:33:51
form, aspects of the cytoskeleton
of the cell. And when we talk about
488
00:33:51 --> 00:33:55
the cytoskeleton we talk about
this network of proteins which,
489
00:33:55 --> 00:34:00
as I said before,
gives the cell rigidity.
490
00:34:00 --> 00:34:04
Keep in mind that the prefix cyto
or the suffix cyt refers always to
491
00:34:04 --> 00:34:08
cells. Allows the cell to have
shape. And here you can see this
492
00:34:08 --> 00:34:12
network as depicted in one way,
but here it's depicted actually much
493
00:34:12 --> 00:34:17
more dramatically. And
here you begin to see the
494
00:34:17 --> 00:34:21
complexity of what exists inside
the cell. Here are these proteins.
495
00:34:21 --> 00:34:25
These are polymers of proteins
called vimentin which are present in
496
00:34:25 --> 00:34:29
very many mesenchymal cells.
Here are microtubules made from
497
00:34:29 --> 00:34:33
another kind of protein.
Here are microfilaments,
498
00:34:33 --> 00:34:37
in this case made of the molecule
actin. And if we looked at
499
00:34:37 --> 00:34:41
individual molecules of
actin they would be invisible.
500
00:34:41 --> 00:34:45
This is end-to-end polymerization
of many actin molecules.
501
00:34:45 --> 00:34:49
And we're looking here under the
microscope from one end of the cell
502
00:34:49 --> 00:34:53
to the other end of the cell. And
you can see how these molecules,
503
00:34:53 --> 00:34:57
they create stiffness, and
they also enable the cell to
504
00:34:57 --> 00:35:00
contract and to move. Some
people might think that the
505
00:35:00 --> 00:35:04
interior of the cell is just water
with some molecules floating around
506
00:35:04 --> 00:35:08
them. But if you actually look
at what's present in the cell,
507
00:35:08 --> 00:35:12
more than 50% of the volume
is taken up by proteins.
508
00:35:12 --> 00:35:16
It's not simply an aqueous solvent
where everything moves around freely.
509
00:35:16 --> 00:35:20
It's a very viscous slush, a
mush. And it's quite difficult
510
00:35:20 --> 00:35:24
there for many cells to move
around from one part of the
511
00:35:24 --> 00:35:27
cell to the other. Here you
begin to get a feeling now
512
00:35:27 --> 00:35:31
for how the connection, which
we'll reinforce shortly in
513
00:35:31 --> 00:35:35
great detail, between individual
molecules and the cytoskeleton.
514
00:35:35 --> 00:35:38
And here you see these actin fibers.
I showed them to you just moments
515
00:35:38 --> 00:35:42
ago stretching from one end
of the cell to the other.
516
00:35:42 --> 00:35:46
And each of these little globules
is a single actin monomer which
517
00:35:46 --> 00:35:50
polymerize end-to-end and then form
multi-strand aggregates to create
518
00:35:50 --> 00:35:54
the actin cytoskeleton. Here's
an intermediate filament and
519
00:35:54 --> 00:35:58
here's the microtubules that are
formed, once again giving us this
520
00:35:58 --> 00:36:03
impression that the cell is actually
highly organized and that that high
521
00:36:03 --> 00:36:07
degree of organization is able to
give it some physical structure and
522
00:36:07 --> 00:36:12
shape and form. I think
we're going to end today
523
00:36:12 --> 36:17
two minutes early. You
probably won't object.